# Immunophenotypic analysis of the cutaneous humoral response in early Lyme disease

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $251,250

## Abstract

PROJECT SUMMARY
Lyme disease, due to infection with the tick-transmitted spirochete Borrelia burgdorferi, is a multisystem disorder
that can present with either localized skin infection or with disseminated infection involving multiple skin sites
and other organs systems, including the heart, nervous system and joints. Humoral immunity is a critical host
defense against B. burgdorferi infection, and a strong early B cell response in the blood is associated with
symptom resolution. B. burgdorferi infection can also trigger autoantibody production and immune dysregulation
associated with autoimmune pathologies. Despite the importance of antibody production to host defense, little is
known about their role in the skin where tick-transmitted spirochetes first establish infection. We have applied
advanced transcriptome technologies to study the sparse B cell populations found in the primary erythema
migrans lesion and nonlesional skin of subjects who presented with localized or disseminated Lyme disease.
Using 10X single cell immune repertoire and gene expression profiling, we identified antibody sequences from
B cells that have the characteristics of a response to an immune challenge such as infection (i.e. clonal
expansion, somatic hypermutation and class switching). These sequences were not present in nonlesional skin,
but in some cases were also found in the blood of the same patient. In preliminary data, we have produced 11
recombinant human monoclonal antibodies (mAb) based on these antibody sequences and to date, have found
that 2 mAb react with a surface exposed Bb antigen, 15-20kD in size. In this proposal, we will expand the
recombinant mAb production and determine if the mAb react with B. burgdorferi or self-antigens. We will use the
newly developed and innovative Rapid Exoproteome Antibody Profiling (REAP) discovery tool for high
throughput screening of recombinant mAb and immune sera for reactivity against proteins in the exoproteome.
Archived sera collected prospectively from Lyme subjects at diagnosis and several time points in convalescence
will be screened for reactivity against identified Bb antigens as well as self antigens over time. The results of
these studies will be the first tissue-specific analysis of the antigen specificity of B cells in early Lyme disease,
and provide insight into the durability of immune responses and capacity of the antibodies to influence infection
outcomes. It may also provide identities of new target antigens for use in diagnostic tests for early Lyme disease
or distinguish new infection from previously treated infections. In addition, these studies may provide insight into
when self-reactivity first arises after B. burgdorferi infection and the evolution of the response to targeted
antigens. Successful completion of these studies will create a model for investigation of the skin B cell response
to other vector-borne pathogens of public health significance.

## Key facts

- **NIH application ID:** 10451111
- **Project number:** 1R21AI153644-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Linda K. Bockenstedt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2022-02-03 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451111

## Citation

> US National Institutes of Health, RePORTER application 10451111, Immunophenotypic analysis of the cutaneous humoral response in early Lyme disease (1R21AI153644-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10451111. Licensed CC0.

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